# Preclinical optimization of a gene therapy for erythromelalgia and chronic pain

> **NIH NIH U44** · NAVEGA THERAPEUTICS, INC. · 2024 · $74,701

## Abstract

Abstract
Currently 1.5 billion people worldwide suffer from chronic pain. This number continues to increase as the
elderly population grows, the prevalence of diabetes rises, and cancer survival rates improve. Chronic pain
not only severely impacts daily quality of life for many patients, but it also places a heavy socioeconomic
burden on society. With a lack of efficacious treatment options available, chronic pain is often treated with
opioids. This is dangerous due to recent understanding of the extremely addictive and detrimental effects
of opioids leading to the current opioid epidemic. Therefore, there is an urgent and clear unmet need for
non-addictive alternative analgesics for the treatment of chronic pain. This need to find a solution to
addictive opioids has brought interest to a particular sodium channel, NaV1.7, shown to be important for
pain sensing. Gain-of-function mutations in NaV1.7 are associated with a disorder characterized by intense
burning pain in the extremities: primary erythromelalgia. Conversely, loss-of function of NaV1.7 results in
the inability to feel pain. Therefore, inhibiting NaV1.7 can be an effective method of reducing pain and treat
erythromelalgia patients. To accomplish this, we designed epigenetic modulators to repress expression of
SCN9A (encoding the NaV1.7 channel). Rather than making permanent edits to the genome, these epigenetic
modulators will transiently inhibit expression of SCN9A. By targeting NaV1.7 at the DNA-level instead of
the protein or RNA level, we can achieve specific and long-lasting modulation of NaV1.7, with better
pharmacokinetics prospects than RNA- and protein-targeting approaches. In the parent CREATE grant, we
propose to optimize these epigenetic modulators as well as their delivery to achieve high specificity and
efficacy. The result of this study will be an optimized gene therapy that is not only non-addictive and
efficacious for treatment of chronic pain but also highly specific and long-lasting. Although there is a clear
market for a non-addictive therapy for chronic pain, we believe that a continued optimization of the AAV
so that it can be delivered systemically instead of intrathecally will expand the patient population. This
supplement will contribute to the optimization of the delivery of the therapy to improve the specificity and
decrease manufacturing costs, which will translate to a more affordable therapy for patients.

## Key facts

- **NIH application ID:** 10983720
- **Project number:** 3U44NS122114-03S1
- **Recipient organization:** NAVEGA THERAPEUTICS, INC.
- **Principal Investigator:** Fernando Aleman Guillen
- **Activity code:** U44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $74,701
- **Award type:** 3
- **Project period:** 2021-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10983720

## Citation

> US National Institutes of Health, RePORTER application 10983720, Preclinical optimization of a gene therapy for erythromelalgia and chronic pain (3U44NS122114-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10983720. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*